1. Field of the Invention
The present invention relates to optical elements, sensor devices, manufacturing method of optical elements, detection elements, target substance measuring devices and detection methods, and in particular, it relates to an optical element for detecting density of a target substance, a sensor device, and a method of manufacturing an optical element.
2. Description of the Related Art
It is known that a minute conductive structure induces Localized Surface Plasmon Resonance (hereinafter referred to as LSPR). This LSPR has its resonance condition decided by refraction index and dielectric constant of the periphery of the conductive structure. Consequently, variation of the dielectric index of the periphery of the conductive structure can be detected as variation of the resonance condition. The variation of the resonance condition can be detected by allowing the light to irradiate and transmit the conductive structure and measure the variation of the optical spectrum.
The LSPR is sensitive to the variations of the refraction index and the dielectric constant of the periphery of the conductive structure. Consequently, the LSPR can be applied to a high sensitive refraction index sensor. Further, as illustrated below, when the variation of this dielectric constant is due to biological reaction, this phenomenon is applied to a biosensor and the like to enable high sensitive sensing, and a wide range of applications can be expected in the fields of medical care, food, environment, and the like.
For example, when an antigen-antibody reaction is allowed to occur in the periphery of the conductive structure, this reaction can be detected. Richard P. Van Duyne et al., NANO LETTERS, Vol. 4, No. 6, pp. 1029-1034, 2004 discloses an example using a minute Ag thin film fine particle structure formed on a smooth substrate as the conductive structure. That is, the literature discloses the case where the periphery of this structure is adhered with an antibody, and a method of measuring an antigen density from the variation of the optical spectrum in a state in which this antibody is further bound to an antigen. Here, it is reported that a refraction index response when the ambient medium is changed is 76.4 nm/index.
In addition, a composite body of oxygen and substrate, a complementary base pairing by DNA-hybridization, and the like can be also similarly detected.
Further, Japanese Patent Application Laid Open No. 2000-356587 discloses a method of fixing Au fine particle on a glass substrate and detecting refraction index of the fine particle periphery from the spectrum of its Plasmon resonance.
Japanese Patent Application Laid Open No. 2004-245639 discloses a problem that the variation of a detection element output signal is feeble, and a detection element for solving the problem that a long period of time is required until such variation is recognized. That is, Japanese Patent Application Laid Open No. 2004-245639 discloses a detection element, in which a plurality of pores are formed on one surface, and a substrate filled with metal fine particles inside the pore is provided, and at least part of the metal fine particles is exposed outside the substrate rather than one surface.
Further, J. Phys. Chem. B 1999, 103, 9846-9853, Nanosphere Lithography: Effect of External Dielectric Medium on the Surface Plasmon Resonance Spectrum of a Periodic Array of Silver Nanoparticle discloses a technique for disposing Ag dots in side-by-side arrangement by using nanosphere lithography (lithography technique using nano beads of polyethylene) and fabricating a LSPR detection element. It is reported that the refraction index response when the ambient medium is changed is 200 nm/index.
In the case of an ordinary transit measurement including the conventional art, the variation of the dielectric constant by an antigen-antibody reaction at the conductive fine particle periphery is detected by measuring a transmission spectrum LSPR optical spectrum (before reaction) 101 and a LSPR optical spectrum (after reaction) 102 of the conductive fine particle before and after the reaction. From the variation of the resonance condition of the LSPR before and after the reaction, an antigen density is detected (FIG. 19A). The outline of the measuring system at this time, similarly to FIG. 19B, is such that a conductive fine particle 103 modified in the surface by an antibody 105 irradiates an irradiated light 107 and a transmitted light 108 to a measuring element 106 supported by a dielectric substrate 104, and measures its transmission spectrum.
Now, as described above, when the variation of the dielectric constant of a metal structure periphery is detected as the variation of an optical spectrum signal using the LSPR, in case the density of a biological substance to be measured is exceptionally low, it is quite probabilistic to which portion of the metal structure surface a measured molecule binds. Hence, the variation of the spectrum signal is different every dot, and the spectrum after being adhered with the biological substance ends up becoming broadened. As a result, a problem arises that the measuring sensitivity is lowered.